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1.
Cell ; 185(11): 1842-1859.e18, 2022 05 26.
Article in English | MEDLINE | ID: mdl-35561686

ABSTRACT

The precise genetic origins of the first Neolithic farming populations in Europe and Southwest Asia, as well as the processes and the timing of their differentiation, remain largely unknown. Demogenomic modeling of high-quality ancient genomes reveals that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Southwest Asian population with a strongly bottlenecked western hunter-gatherer population after the last glacial maximum. Moreover, the ancestors of the first farmers of Europe and Anatolia went through a period of extreme genetic drift during their westward range expansion, contributing highly to their genetic distinctiveness. This modeling elucidates the demographic processes at the root of the Neolithic transition and leads to a spatial interpretation of the population history of Southwest Asia and Europe during the late Pleistocene and early Holocene.


Subject(s)
Farmers , Genome , Agriculture , DNA, Mitochondrial/genetics , Europe , Genetic Drift , Genomics , History, Ancient , Human Migration , Humans
2.
Nature ; 618(7965): 557-565, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37198485

ABSTRACT

Centromeres are critical for cell division, loading CENH3 or CENPA histone variant nucleosomes, directing kinetochore formation and allowing chromosome segregation1,2. Despite their conserved function, centromere size and structure are diverse across species. To understand this centromere paradox3,4, it is necessary to know how centromeric diversity is generated and whether it reflects ancient trans-species variation or, instead, rapid post-speciation divergence. To address these questions, we assembled 346 centromeres from 66 Arabidopsis thaliana and 2 Arabidopsis lyrata accessions, which exhibited a remarkable degree of intra- and inter-species diversity. A. thaliana centromere repeat arrays are embedded in linkage blocks, despite ongoing internal satellite turnover, consistent with roles for unidirectional gene conversion or unequal crossover between sister chromatids in sequence diversification. Additionally, centrophilic ATHILA transposons have recently invaded the satellite arrays. To counter ATHILA invasion, chromosome-specific bursts of satellite homogenization generate higher-order repeats and purge transposons, in line with cycles of repeat evolution. Centromeric sequence changes are even more extreme in comparison between A. thaliana and A. lyrata. Together, our findings identify rapid cycles of transposon invasion and purging through satellite homogenization, which drive centromere evolution and ultimately contribute to speciation.


Subject(s)
Arabidopsis , Centromere , DNA Transposable Elements , DNA, Satellite , Evolution, Molecular , Arabidopsis/genetics , Arabidopsis/metabolism , Centromere/genetics , Centromere/metabolism , DNA Transposable Elements/genetics , Histones/genetics , Histones/metabolism , Nucleosomes/genetics , Nucleosomes/metabolism , DNA, Satellite/genetics , Gene Conversion
3.
Nature ; 606(7914): 565-569, 2022 06.
Article in English | MEDLINE | ID: mdl-35650430

ABSTRACT

Flowering plants (angiosperms) can grow at extreme altitudes, and have been observed growing as high as 6,400 metres above sea level1,2; however, the molecular mechanisms that enable plant adaptation specifically to altitude are unknown. One distinguishing feature of increasing altitude is a reduction in the partial pressure of oxygen (pO2). Here we investigated the relationship between altitude and oxygen sensing in relation to chlorophyll biosynthesis-which requires molecular oxygen3-and hypoxia-related gene expression. We show that in etiolated seedlings of angiosperm species, steady-state levels of the phototoxic chlorophyll precursor protochlorophyllide are influenced by sensing of atmospheric oxygen concentration. In Arabidopsis thaliana, this is mediated by the PLANT CYSTEINE OXIDASE (PCO) N-degron pathway substrates GROUP VII ETHYLENE RESPONSE FACTOR transcription factors (ERFVIIs). ERFVIIs positively regulate expression of FLUORESCENT IN BLUE LIGHT (FLU), which represses the first committed step of chlorophyll biosynthesis, forming an inactivation complex with tetrapyrrole synthesis enzymes that are negatively regulated by ERFVIIs, thereby suppressing protochlorophyllide. In natural populations representing diverse angiosperm clades, we find oxygen-dependent altitudinal clines for steady-state levels of protochlorophyllide, expression of inactivation complex components and hypoxia-related genes. Finally, A. thaliana accessions from contrasting altitudes display altitude-dependent ERFVII activity and accumulation. We thus identify a mechanism for genetic adaptation to absolute altitude through alteration of the sensitivity of the oxygen-sensing system.


Subject(s)
Acclimatization , Altitude , Arabidopsis , Oxygen , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Chlorophyll/metabolism , Gene Expression Regulation, Plant , Oxygen/metabolism , Partial Pressure , Protochlorophyllide/metabolism
4.
PLoS Biol ; 21(7): e3002191, 2023 07.
Article in English | MEDLINE | ID: mdl-37463141

ABSTRACT

We study natural DNA polymorphisms and associated phenotypes in the Arabidopsis relative Cardamine hirsuta. We observed strong genetic differentiation among several ancestry groups and broader distribution of Iberian relict strains in European C. hirsuta compared to Arabidopsis. We found synchronization between vegetative and reproductive development and a pervasive role for heterochronic pathways in shaping C. hirsuta natural variation. A single, fast-cycling ChFRIGIDA allele evolved adaptively allowing range expansion from glacial refugia, unlike Arabidopsis where multiple FRIGIDA haplotypes were involved. The Azores islands, where Arabidopsis is scarce, are a hotspot for C. hirsuta diversity. We identified a quantitative trait locus (QTL) in the heterochronic SPL9 transcription factor as a determinant of an Azorean morphotype. This QTL shows evidence for positive selection, and its distribution mirrors a climate gradient that broadly shaped the Azorean flora. Overall, we establish a framework to explore how the interplay of adaptation, demography, and development shaped diversity patterns of 2 related plant species.


Subject(s)
Arabidopsis , Cardamine , Arabidopsis/genetics , Cardamine/genetics , Genotype , Phenotype , Demography
5.
Plant Physiol ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38606947

ABSTRACT

Natural variation in trichome pattern (amount and distribution) is prominent among populations of many angiosperms. However, the degree of parallelism in the genetic mechanisms underlying this diversity and its environmental drivers in different species remain unclear. To address these questions, we analyzed the genomic and environmental bases of leaf trichome pattern diversity in Cardamine hirsuta, a relative of Arabidopsis (Arabidopsis thaliana). We characterized 123 wild accessions for their genomic diversity, leaf trichome patterns at different temperatures, and environmental adjustments. Nucleotide diversities and biogeographical distribution models identified two major genetic lineages with distinct demographic and adaptive histories. Additionally, C. hirsuta showed substantial variation in trichome pattern and plasticity to temperature. Trichome amount in C. hirsuta correlated positively with spring precipitation but negatively with temperature, which is opposite to climatic patterns in A. thaliana. Contrastingly, genetic analysis of C. hirsuta glabrous accessions indicated that, like for A. thaliana, glabrousness is caused by null mutations in ChGLABRA1 (ChGL1). Phenotypic genome-wide association studies (GWAS) further identified a ChGL1 haplogroup associated with low trichome density and ChGL1 expression. Therefore, a ChGL1 series of null and partial loss-of-function alleles accounts for the parallel evolution of leaf trichome pattern in C. hirsuta and A. thaliana. Finally, GWAS also detected other candidate genes (e.g. ChETC3, ChCLE17) that might affect trichome pattern. Accordingly, the evolution of this trait in C. hirsuta and A. thaliana shows partially conserved genetic mechanisms but is likely involved in adaptation to different environments.

6.
Ann Intern Med ; 177(3): 353-362, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38316009

ABSTRACT

BACKGROUND: In addition to the physical disease burden of the COVID-19 pandemic, concern exists over its adverse mental health effects. OBJECTIVE: To characterize trends in psychological distress and outpatient mental health care among U.S. adults from 2018 to 2021 and to describe patterns of in-person, telephone, and video outpatient mental health care. DESIGN: Cross-sectional nationally representative survey of noninstitutionalized adults. SETTING: United States. PARTICIPANTS: Adults included in the Medical Expenditure Panel Survey Household Component, 2018 to 2021 (n = 86 658). MEASUREMENTS: Psychological distress was measured with the Kessler-6 scale (range of 0 to 24, with higher scores indicating more severe distress), with a score of 13 or higher defined as serious psychological distress, 1 to 12 as less serious distress, and 0 as no distress. Outpatient mental health care use was measured via computer-assisted personal interviews. RESULTS: Between 2018 and 2021, the rate of serious psychological distress among adults increased from 3.5% to 4.2%. Although the rate of outpatient mental health care increased from 11.2% to 12.4% overall, the rate decreased from 46.5% to 40.4% among adults with serious psychological distress. When age, sex, and distress were controlled for, a significant increase in outpatient mental health care was observed for young adults (aged 18 to 44 years) but not middle-aged (aged 45 to 64 years) and older (aged >65 years) adults and for employed adults but not unemployed adults. In 2021, 33.4% of mental health outpatients received at least 1 video visit, including a disproportionate percentage of young, college-educated, higher-income, employed, and urban adults. LIMITATION: Information about outpatient mental health service modality (in-person, video, telephone) was first fully available in the 2021 survey. CONCLUSION: These trends and patterns underscore the persistent challenges of connecting older adults, unemployed persons, and seriously distressed adults to outpatient mental health care and the difficulties faced by older, less educated, lower-income, unemployed, and rural patients in accessing outpatient mental health care via video. PRIMARY FUNDING SOURCE: None.


Subject(s)
COVID-19 , Psychological Distress , Young Adult , Humans , United States/epidemiology , Aged , Adolescent , Adult , Outpatients , Mental Health , COVID-19/epidemiology , Cross-Sectional Studies , Pandemics , Stress, Psychological/epidemiology , Stress, Psychological/psychology
7.
Breast Cancer Res Treat ; 205(2): 249-256, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38376796

ABSTRACT

PURPOSE: Depression is among the most common comorbid psychiatric disorders of patients with breast cancer. Depression decreases patient quality of life and, if untreated, can adversely affect cancer treatment. We sought to identify treatment barriers for women with breast cancer receiving psychotherapy for depression. Findings may help policy makers and researchers determine funding and design of future studies involving this population, especially in communities with high rates of health disparities. METHODS: We used data from a randomized trial for women with breast cancer and current DSM-IV non-psychotic unipolar major depressive disorder (MDD). Patients were randomly assigned to 12 weeks of one of three psychotherapies and attrition was assessed by whether subjects completed 12 weekly treatment sessions. We used descriptive analyses and logistic regression to identify treatment barriers. R shiny was used to determine study patient residences. RESULTS: Of 134 randomized patients, 84 (62.7%) were Hispanic. Fifty-nine patients (44%) either did not start or dropped out of treatment, 49 (83.1%) of them being Hispanic. Being a Hispanic woman, less educated, and geographically distant from treatment significantly predicted attrition. Single Hispanic mothers had significantly higher attrition risk than married and/or childless women. CONCLUSION: Identifying barriers to treatment is important to improve treatment adherence for patients with concurrent diagnoses of breast cancer and MDD, especially for traditionally underserved minorities. Additional support such as affordable tele-medicine, multi-language assistance, financial aid for transportation and child-care, and allocation of more funds to address some identified barriers deserve consideration to improve treatment adherence and outcomes.


Subject(s)
Breast Neoplasms , Comorbidity , Depressive Disorder, Major , Hispanic or Latino , Humans , Female , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Breast Neoplasms/epidemiology , Breast Neoplasms/complications , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/therapy , Hispanic or Latino/statistics & numerical data , Hispanic or Latino/psychology , Middle Aged , Adult , Aged , Psychotherapy/methods , Health Services Accessibility , Quality of Life
8.
Plant Cell ; 33(3): 548-565, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33955486

ABSTRACT

Both inter- and intra-specific diversity has been described for trichome patterning in fruits, which is presumably involved in plant adaptation. However, the mechanisms underlying this developmental trait have been hardly addressed. Here we examined natural populations of Arabidopsis (Arabidopsis thaliana) that develop trichomes in fruits and pedicels, phenotypes previously not reported in the Arabidopsis genus. Genetic analyses identified five loci, MALAMBRUNO 1-5 (MAU1-5), with MAU2, MAU3, and MAU5 showing strong epistatic interactions that are necessary and sufficient to display these traits. Functional characterization of these three loci revealed cis-regulatory mutations in TRICHOMELESS1 and TRIPTYCHON, as well as a structural mutation in GLABRA1. Therefore, the multiple mechanisms controlled by three MYB transcription factors of the core regulatory network for trichome patterning have jointly been modulated to trigger trichome development in fruits. Furthermore, analyses of worldwide accessions showed that these traits and mutations only occur in a highly differentiated relict lineage from the Iberian Peninsula. In addition, these traits and alleles were associated with low spring precipitation, which suggests that trichome development in fruits and pedicels might be involved in climatic adaptation. Thus, we show that the combination of synergistic mutations in a gene regulatory circuit has driven evolutionary innovations in fruit trichome patterning in Arabidopsis.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Fruit/metabolism , Proto-Oncogene Proteins c-myb/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Fruit/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Mutation/genetics , Proto-Oncogene Proteins c-myb/genetics
9.
Allergy ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864116

ABSTRACT

BACKGROUND: Allergic diseases begin early in life and are often chronic, thus creating an inflammatory environment that may precede or exacerbate other pathologies. In this regard, allergy has been associated to metabolic disorders and with a higher risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. METHODS: We used a murine model of allergy and atherosclerosis, different diets and sensitization methods, and cell-depleting strategies to ascertain the contribution of acute and late phase inflammation to dyslipidemia. Untargeted lipidomic analyses were applied to define the lipid fingerprint of allergic inflammation at different phases of allergic pathology. Expression of genes related to lipid metabolism was assessed in liver and adipose tissue at different times post-allergen challenge. Also, changes in serum triglycerides (TGs) were evaluated in a group of 59 patients ≥14 days after the onset of an allergic reaction. RESULTS: We found that allergic inflammation induces a unique lipid signature that is characterized by increased serum TGs and changes in the expression of genes related to lipid metabolism in liver and adipose tissue. Alterations in blood TGs following an allergic reaction are independent of T-cell-driven late phase inflammation. On the contrary, the IgG-mediated alternative pathway of anaphylaxis is sufficient to induce a TG increase and a unique lipid profile. Lastly, we demonstrated an increase in serum TGs in 59 patients after undergoing an allergic reaction. CONCLUSION: Overall, this study reveals that IgG-mediated allergic inflammation regulates lipid metabolism.

10.
Macromol Rapid Commun ; : e2400091, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38690992

ABSTRACT

Within bioplastics, natural poly(3-hydroxybutyrate) (PHB) stands out as fully biocompatible and biodegradable, even in marine environments; however, its high isotacticity and crystallinity limits its mechanical properties and hence its applications. PHB can also be synthesized with different tacticities via a catalytic ring-opening polymerization (ROP) of rac-ß-butyrolactone (BBL), paving the way to PHB with better thermomechanical and processability properties. In this work, the catalyst family is extended based on aluminum phenoxy-imine methyl catalyst [AlMeL2], that reveals efficient in the ROP of BBL, to the halogeno analogous complex [AlClL2]. As well, the impact on the ROP mechanism of different initiators is further explored with a particular focus in dimethylaminopyridine (DMAP), a hardly studied initiator for the ROP of BBL. A thorough mechanistic study is performed that evidences the presence of two concomitant DMAP-mediated mechanisms, that lead to either a DMAP or a crotonate end-capping group. Besides, in order to increase the possibilities of PHB post-polymerization functionalization, the introduction of a side-chain functionality is explored, establishing the copolymerization of BBL with ß-allyloxymethylene propiolactone (BPLOAll), resulting in well-defined P(BBL-co-BPLOAll) copolymers.

11.
Ann Intern Med ; 176(8): 1081-1088, 2023 08.
Article in English | MEDLINE | ID: mdl-37549391

ABSTRACT

BACKGROUND: Despite an unprecedented increase in drug overdose deaths in the United States, the risks faced by U.S. health care workers, who often have access to controlled prescription drugs, are not known. OBJECTIVE: To estimate risks for drug overdose death among health care workers relative to non-health care workers. DESIGN: Prospective cohort study. SETTING: United States. PARTICIPANTS: Health care workers (n = 176 000) and non-health care workers (n = 1 662 000) aged 26 years or older surveyed in 2008 and followed for cause of death through 2019. MEASUREMENTS: Age- and sex-standardized drug overdose deaths were determined for 6 health care worker groups (physicians, registered nurses, other treating or diagnosing health care workers, health technicians, health care support workers, and social or behavioral health workers) and non-health care workers. Adjusted drug overdose death hazards (and 95% CIs) were also evaluated, with adjustment for age, sex, race/ethnicity, marital status, education, income, urban or rural residence, and region. RESULTS: Approximately 0.07% of our study sample died of a drug overdose during follow-up. Among health care workers, annual standardized rates of drug overdose death per 100 000 persons ranged from 2.3 (95% CI, 0 to 4.8) for physicians to 15.5 (CI, 9.8 to 21.2) for social or behavioral health workers. Compared with those for non-health care workers, the adjusted hazards of total drug overdose death were significantly increased for social or behavioral health workers (adjusted hazard ratio, 2.55 [CI, 1.74 to 3.73]), registered nurses (adjusted hazard ratio, 2.22 [CI, 1.57 to 3.13]), and health care support workers (adjusted hazard ratio, 1.60 [CI, 1.19 to 2.16]), but not for physicians (adjusted hazard ratio, 0.61 [CI, 0.19 to 1.93]), other treating or diagnosing health care workers (adjusted hazard ratio, 0.93 [CI, 0.44 to 1.95]), or health technicians (adjusted hazard ratio, 1.13 [CI, 0.75 to 1.68]). Results were generally similar for opioid-related overdose deaths and unintentional overdose deaths. LIMITATION: Unmeasured confounding, uncertain validity of cause of death, and one-time assessment of occupation. CONCLUSION: Registered nurses, social or behavioral health workers, and health care support workers were at increased risk for drug overdose death, suggesting the need to identify and intervene on those at high risk. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.


Subject(s)
Drug Overdose , Opiate Overdose , Prescription Drugs , Humans , United States/epidemiology , Cohort Studies , Prospective Studies , Health Personnel , Analgesics, Opioid/adverse effects
12.
Psychol Med ; 53(8): 3406-3415, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35125124

ABSTRACT

BACKGROUND: Most psychiatric disorders are associated with several risk factors, but a few underlying psychopathological dimensions account for the common co-occurrence of disorders. If these underlying psychopathological dimensions mediate associations of the risk factors with psychiatric disorders, it would support a trans-diagnostic orientation to etiological research and treatment development. METHOD: An analysis was performed of the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III), a US nationally representative sample of non-institutionalized civilian adults, focusing on respondents who were aged ⩾21 (n = 34 712). Structural equation modeling was used to identify the psychopathological dimensions underlying psychiatric disorders; to examine associations between risk factors, psychopathological dimensions and individual disorders; and to test whether associations of risk factors occurring earlier in life were mediated by risk factors occurring later in life. RESULTS: A bifactor model of 13 axis I disorders provided a good fit (CFI = 0.987, TLI = 0.982, and RMSEA = 0.011) including an overall psychopathology factor as measured by all 13 disorders and 2 specific factors, one for externalizing disorders and one for fear-related disorders. A substantial proportion of the total effects of the risk factors occurring early in life were indirectly mediated through factors occurring later in life. All risk factors showed a significant total effect on the general psychopathology, externalizing and fear-related factors. Only 23 of 325 direct associations of risk factors with psychiatric disorders achieved statistical significance. CONCLUSION: Most risk factors for psychiatric disorders are mediated through broad psychopathological dimensions. The central role of these dimensions supports trans-diagnostic etiological and intervention research.


Subject(s)
Alcohol-Related Disorders , Mental Disorders , Adult , Humans , Aged , Mental Disorders/psychology , Psychopathology , Fear , Risk Factors
13.
Mol Psychiatry ; 27(2): 787-792, 2022 02.
Article in English | MEDLINE | ID: mdl-34716409

ABSTRACT

The evolving nature of the opioid epidemic and continued increases in overdose deaths highlight a need for fundamental change in the collection and use of surveillance data to link them to implementation of effective service, treatment, and prevention approaches. Yet at present, the quality and timeliness of US surveillance data often limits data-driven approaches. We review current information needs, summarize limitations of existing data, propose complementary surveillance resources, and provide examples of promising approaches designed to meet the needs of data end-users. We conclude that there is a need for an approach that focuses on the needs of data end-users, such as public health systems leaders, policy makers, public, nonprofit and prepaid healthcare systems, and other systems, such as the justice system. Such an approach, which may require investments in new infrastructure, should prioritize improvements in data timeliness, sample representativeness, database linkage, and increased flexibility to adapt to shifts in the environment, while preserving the privacy of survey participants. Use of simulations, distributed research and data networks, alternative data sources, such as wastewater or digital data collection and use of blockchain technology, are some of promising avenues toward an improved and more user-centered surveillance system.


Subject(s)
Analgesics, Opioid , Drug Overdose , Analgesics, Opioid/adverse effects , Humans , Opioid Epidemic
14.
Eur Arch Psychiatry Clin Neurosci ; 273(3): 627-638, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35723739

ABSTRACT

Prior research suggests that certain psychiatric symptoms could be associated with increased risk of death. However, it remains unclear whether this association could rely on all or specific symptoms. In this report, we used data from a multicenter 5-year prospective study (N = 641) of older adults with an ICD-10 diagnosis of schizophrenia, bipolar disorder or major depressive disorder, recruited from French community psychiatric departments. We used a latent variable approach to disentangle the effects shared by all psychiatric symptoms (i.e., general psychopathology factor) and those specific to individual psychiatric symptoms, while adjusting for sociodemographic and clinical factors. Psychiatric symptoms were assessed face-to-face by psychiatrists trained to semi-structured interviews using the Brief Psychiatric Rating Scale (BPRS). Among older adults with major psychiatric disorders, we found that all psychiatric symptoms were associated with increased mortality, and that their effect on the 5-year mortality were exerted mostly through a general psychopathology dimension (ß = 0.13, SE = 0.05, p < 0.05). No BPRS item or lower order factor had a significant effect on mortality beyond and above the effect of the general psychopathology factor. Greater number of medical conditions, older age, male sex, and being hospitalized or institutionalized at baseline were significantly associated with this risk beyond the effect of the general psychopathology factor. Since psychiatric symptoms may affect mortality mainly through a general psychopathology dimension, biological and psychological mechanisms underlying this dimension should be considered as promising targets for interventions to decrease excess mortality of older individuals with psychiatric disorders.


Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Mental Disorders , Schizophrenia , Humans , Male , Aged , Prospective Studies , Mental Disorders/diagnosis
15.
Aging Ment Health ; 27(9): 1752-1761, 2023.
Article in English | MEDLINE | ID: mdl-36905630

ABSTRACT

OBJECTIVE: Prior studies report conflicting results about the association between lithium use and all-cause mortality. In addition, data are scarce on this association among older adults with psychiatric disorders. In this report, we sought to examine the associations of lithium use with all-cause mortality and specific causes of death (i.e., due to cardiovascular disorder, non-cardiovascular disease, accident, or suicide) among older adults with psychiatric disorders during a 5-year follow-up period. METHODS: In this observational epidemiological study, we used data from 561 patients belonging to a Cohort of individuals with Schizophrenia or Affective disorders aged 55-years or more (CSA). Patients taking lithium at baseline were first compared to patients not taking lithium, and then to patients taking (i) antiepileptics and (ii) atypical antipsychotics in sensitivity analyses. Analyses were adjusted for socio-demographic (e.g., age, gender), clinical characteristics (e.g., psychiatric diagnosis, cognitive functioning), and other psychotropic medications (e.g. benzodiazepines). RESULTS: There was no significant association between lithium use and all-cause mortality [AOR=1.12; 95%CI=0.45-2.79; p=0.810] or disease-related mortality [AOR=1.37; 95%CI=0.51-3.65; p=0.530]. None of the 44 patients taking lithium died from suicide, whereas 4.0% (N=16) of patients not receiving lithium did. CONCLUSION: These findings suggest that lithium may not be associated with all-cause or disease-related mortality and might be associated with reduced risk of suicide in this population. They argue against the underuse of lithium as compared with antiepileptics and atypical antipsychotics among older adults with mood disorders.


Subject(s)
Lithium , Mental Disorders , Humans , Anticonvulsants/therapeutic use , Antipsychotic Agents/therapeutic use , Lithium/adverse effects , Lithium/therapeutic use , Mental Disorders/drug therapy , Prospective Studies , Middle Aged
16.
Prev Sci ; 24(Suppl 1): 8-15, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37603259

ABSTRACT

Launched in 2018, the National Institutes of Health (NIH) Helping to End Addiction Long-term Initiative®, or NIH HEAL Initiative, is an aggressive effort to speed scientific solutions to stem this national public health crisis. Investments in new strategies to prevent opioid misuse are a key component of this comprehensive response to the opioid epidemic. In 2019, funded through the NIH HEAL Initiative® and administered by the National Institute on Drug Abuse (NIDA), HEAL Preventing Opioid Use Disorder (HEAL Preventing OUD) research program began, filling the gap of needed upstream prevention interventions. The vision for HEAL Preventing OUD is that: Healthcare organizations and public systems will be able to make evidence-based preventive intervention services accessible to all persons who experience risk for opioid and other substance misuse or use disorder. Realizing this vision will require research investments in four strategic areas: (1) risk identification; (2) intervention development; (3) social determinants, health equity, and policy; and (4) dissemination, implementation, scale up, and sustainment. There exists tremendous potential for prevention to be a viable solution for the ongoing opioid crisis, particularly through investments in upstream, equitable, and sustainable prevention services.


Subject(s)
Behavior, Addictive , Opioid-Related Disorders , United States , Humans , Opioid-Related Disorders/prevention & control , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Analgesics, Opioid , National Institutes of Health (U.S.) , Public Health
17.
Sensors (Basel) ; 23(16)2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37631602

ABSTRACT

Automatic hand gesture recognition in video sequences has widespread applications, ranging from home automation to sign language interpretation and clinical operations. The primary challenge lies in achieving real-time recognition while managing temporal dependencies that can impact performance. Existing methods employ 3D convolutional or Transformer-based architectures with hand skeleton estimation, but both have limitations. To address these challenges, a hybrid approach that combines 3D Convolutional Neural Networks (3D-CNNs) and Transformers is proposed. The method involves using a 3D-CNN to compute high-level semantic skeleton embeddings, capturing local spatial and temporal characteristics of hand gestures. A Transformer network with a self-attention mechanism is then employed to efficiently capture long-range temporal dependencies in the skeleton sequence. Evaluation of the Briareo and Multimodal Hand Gesture datasets resulted in accuracy scores of 95.49% and 97.25%, respectively. Notably, this approach achieves real-time performance using a standard CPU, distinguishing it from methods that require specialized GPUs. The hybrid approach's real-time efficiency and high accuracy demonstrate its superiority over existing state-of-the-art methods. In summary, the hybrid 3D-CNN and Transformer approach effectively addresses real-time recognition challenges and efficient handling of temporal dependencies, outperforming existing methods in both accuracy and speed.


Subject(s)
Electric Power Supplies , Gestures , Automation , Neural Networks, Computer , Skeleton
18.
Sensors (Basel) ; 23(6)2023 Mar 22.
Article in English | MEDLINE | ID: mdl-36992039

ABSTRACT

Along with society's development, transportation has become a key factor in human daily life, increasing the number of vehicles on the streets. Consequently, the task of finding free parking slots in metropolitan areas can be dramatically challenging, increasing the chance of getting involved in an accident and the carbon footprint, and negatively affecting the driver's health. Therefore, technological resources to deal with parking management and real-time monitoring have become key players in this scenario to speed up the parking process in urban areas. This work proposes a new computer-vision-based system that detects vacant parking spaces in challenging situations using color imagery processed by a novel deep-learning algorithm. This is based on a multi-branch output neural network that maximizes the contextual image information to infer the occupancy of every parking space. Every output infers the occupancy of a specific parking slot using all the input image information, unlike existing approaches, which only use a neighborhood around every slot. This allows it to be very robust to changing illumination conditions, different camera perspectives, and mutual occlusions between parked cars. An extensive evaluation has been performed using several public datasets, proving that the proposed system outperforms existing approaches.

19.
JAMA ; 330(12): 1161-1166, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37750880

ABSTRACT

Importance: Historically elevated risks of suicide among physicians may have declined in recent decades. Yet there remains a paucity of information concerning suicide risks among other health care workers. Objective: To estimate risks of death by suicide among US health care workers. Design, Setting, and Participants: Cohort study of a nationally representative sample of workers from the 2008 American Community Survey (N = 1 842 000) linked to National Death Index records through December 31, 2019. Main Outcomes and Measures: Age- and sex-standardized suicide rates were estimated for 6 health care worker groups (physicians, registered nurses, other health care-diagnosing or treating practitioners, health technicians, health care support workers, social/behavioral health workers) and non-health care workers. Cox models estimated hazard ratios (HRs) of suicide for health care workers compared with non-health care workers using adjusted HRs for age, sex, race and ethnicity, marital status, education, and urban or rural residence. Results: Annual standardized suicide rates per 100 000 persons (median age, 44 [IQR, 35-53] years; 32.4% female [among physicians] to 91.1% [among registered nurses]) were 21.4 (95% CI, 15.4-27.4) for health care support workers, 16.0 (95% CI, 9.4-22.6) for registered nurses, 15.6 (95% CI, 10.9-20.4) for health technicians, 13.1 (95% CI, 7.9-18.2) for physicians, 10.1 (95% CI, 6.0-14.3) for social/behavioral health workers, 7.6 (95% CI, 3.7-11.5) for other health care-diagnosing or treating practitioners, and 12.6 (95% CI, 12.1-13.1) for non-health care workers. The adjusted hazards of suicide were increased for health care workers overall (adjusted HR, 1.32 [95% CI, 1.13-1.54]), health care support workers (adjusted HR, 1.81 [95% CI, 1.35-2.42]), registered nurses (adjusted HR, 1.64 [95% CI, 1.21-2.23]), and health technicians (adjusted HR, 1.39 [95% CI, 1.02-1.89]), but adjusted hazards of suicide were not increased for physicians (adjusted HR, 1.11 [95% CI, 0.71-1.72]), social/behavioral health workers (adjusted HR, 1.14 [95% CI, 0.75-1.72]), or other health care-diagnosing or treating practitioners (adjusted HR, 0.61 [95% CI, 0.36-1.03) compared with non-health care workers (reference). Conclusions: Relative to non-health care workers, registered nurses, health technicians, and health care support workers in the US were at increased risk of suicide. New programmatic efforts are needed to protect the mental health of these US health care workers.


Subject(s)
Health Personnel , Mental Health , Suicide , Adult , Female , Humans , Male , Cohort Studies , Data Collection , Health Personnel/psychology , Health Personnel/statistics & numerical data , Suicide/statistics & numerical data , Risk , United States/epidemiology
20.
Int J Mol Sci ; 24(4)2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36834906

ABSTRACT

Ribosome biogenesis is a complex and multistep process that depends on various assembly factors. To understand this process and identify the ribosome assembly intermediates, most studies have set out to delete or deplete these assembly factors. Instead, we took advantage of the impact of heat stress (45 °C) on the late stages of the biogenesis of the 30S ribosomal subunit to explore authentic precursors. Under these conditions, reduced levels of the DnaK chaperone proteins devoted to ribosome assembly lead to the transient accumulation of 21S ribosomal particles, which are 30S precursors. We constructed strains with different affinity tags on one early and one late 30S ribosomal protein and purified the 21S particles that form under heat shock. A combination of relative quantification using mass spectrometry-based proteomics and cryo-electron microscopy (cryo-EM) was then used to determine their protein contents and structures.


Subject(s)
Escherichia coli Proteins , Escherichia coli , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , HSP70 Heat-Shock Proteins/metabolism , Cryoelectron Microscopy , Ribosomes/metabolism , Ribosomal Proteins/metabolism , Heat-Shock Response
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